scTranslation: A Comprehensive Benchmark for Single-Cell Multi-Omics Modality Translation

Spatial transcriptomics (ST) is a powerful tool for exploring biological properties dependent on structure, proximity, and interaction in tissue. The methods underpinning ST are developing rapidly but are limited in their ability to profile many thousands of genes at a subcellular scale. Although dissociated from tissue, it is known that the whole-transcriptome readouts of cells in single-cell RNA sequencing (scRNA-seq) retain information about their former in situ neighbourhoods, motivating computational methods to recover it. While paired ST and scRNA-seq datasets are scarce, each modality in its own right is abundantly available. We therefore propose to perform cross-modal translation between unpaired ST and scRNA-seq data. In this work we show that a single-cell foundation model can perform this translation via adversarial fine-tuning. We demonstrate that our method performs favourably against methods built for multi-omics translation.

Single-cell studies require analysts to convert raw measurements into specific biological claims through multi-step workflows and integration of metadata, assay context, and auxiliary evidence. Existing AI-biology benchmarks largely measure broad knowledge, executable workflows, or local analysis steps. We introduce scBench-Long, a benchmark for long-horizon single-cell biology in which agents must recover scientific conclusions from raw or near-raw data without prescribed methods. The benchmark contains 21 evaluations spanning melanoma CD8 T-cell reactivity, CD8 RNA+ATAC regulatory inference, human--monkey chimera development, KRAS-driven lung tumor aging, and lethal COVID-19 lung pathology. Tasks cover paired scRNA/TCR sequencing, RNA and chromatin profiling, cross-species transcriptomics, combinatorial scRNA-seq, single-nucleus RNA-seq, immune repertoires, ortholog maps, ligand--receptor resources, and validation evidence. Candidate claims are reproduced, reviewed, and converted into controlled answer vocabularies with deterministic grading and trajectory rubrics. Across 1,068 completed trajectories, the strongest model--harness pair passes 16/63 runs (25.4%). scBench-Long evaluates whether agents can move beyond local analysis steps and make complex scientific claims that are supported by single-cell data.

Interpreting transcriptomic data is one of the most common analytical tasks in modern biology. Yet most current models either consume expression profiles without producing natural-language biological explanations, or reason in language without direct access to quantitative omics measurements. We introduce OmicsLM, a multimodal LLM that connects quantitative omics profiles with natural-language biological tasks. OmicsLM represents each transcriptomic profile as a compact continuous representation within the LLM context. This interface preserves quantitative expression signal while allowing natural-language instructions, explicit gene mentions, and multiple interleaved biological samples to be processed together in one model context. We train OmicsLM on more than 5.5 million instruction-following examples spanning over 70 task types, combining continuous transcriptomic inputs, experimental data rendered through diverse language templates, and free-text biological knowledge and question-answering data. This mixture covers cell type annotation, perturbation prediction, clinical prediction, pathway reasoning, and open-ended biological question answering. Existing benchmarks evaluate either profile-level prediction or text-only biological QA, leaving language-guided, multi-sample reasoning over real expression profiles unmeasured. To close this gap, we introduce GEO-OmicsQA, a benchmark for multi-sample biological question answering built from real Gene Expression Omnibus (GEO) studies. We demonstrate that OmicsLM can use expression profiles directly and perform comparably to specialized omics models on profile-level tasks, while outperforming both omics-specialized models and general LLMs on language-guided biological reasoning over expression data.